title: In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition.
abstract: The in vitro CYP3A4 inhibition profiles of Echinacea purpurea, St. John's wort and ketoconazole were evaluated by three different substrates: 7-benzyloxy-trifluoromethylcoumarin (BFC), 7-benzyloxyquinoline (BQ) and testosterone. St. John's wort and ketoconazole produced similar inhibition profiles regardless of substrate. For E. purpurea, testosterone metabolism showed a much lower CYP3A4 inhibition (IC(50) 5394 microg/ml) compared to the fluorescent substrates BFC and BQ (IC(50) 354 and 452 mg/ml, respectively). It is suggested that the substrate/assay-dependent effects may arise from a complex nature of E. purpurea constituents, involving different CYP3A4 substrate binding sites. The choice of substrate might thus be essential for evaluation of the inhibition of CYP3A4 metabolism for some herbs. A weak inhibition potential of E. purpurea towards CYP3A4-mediated metabolism in vitro was confirmed by the use of three different substrates.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. torsth@alumni.ntnu.no
authors.forename: Torstein Schrøder
authors.initials: TS
authors.lastname: Hansen
authors.forename: Odd Georg
authors.initials: OG
authors.lastname: Nilsen
mesh_terms: D001665:Binding Sites; D003374:Coumarins / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects* / Q000378:metabolism; D020900:Echinacea / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007654:Ketoconazole / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: C419147:7-benzyloxy-4-trifluoromethylcoumarin; D003374:Coumarins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011804:Quinolines; C065956:7-benzyloxyquinoline; D013739:Testosterone; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D007654:Ketoconazole